Antibody‐conjugated MHC class I tetramers can target tumor cells for specific lysis by T lymphocytes

To demonstrate that antibody‐guided targeting of antigenic MHC class I‐peptide tetramer on tumor cells can render them susceptible to lysis by relevant cytotoxic T lymphocytes (CTL), biotinylated HLA‐A*0201/Flu matrix peptide complexes were tetramerized on streptavidin molecules previously coupled to Fab' fragments from monoclonal antibodies (mAb) specific for cell surface markers such as carcinoembryonic antigen (CEA), ErbB‐2 or CD20. Flow cytometry analysis showed that coating of the HLA‐A2‐peptide complexes on the four HLA‐A2‐negative human cancer lines tested (including a CEA‐positive colon carcinoma, an ErbB‐2+ breast carcinoma and two CD20+ B lymphomas) was entirely dependent upon the specificity of the conjugated antibody fragments. More importantly, HLA‐A2‐restricted Flu matrix peptide‐specific CTL were then found to lyse specifically and efficiently the MHC‐coated target cells. These results open the way to the development of new immunotherapy strategies based on antibody targeting of MHC class I‐peptide complexes.